Bioterrorism The New Threat by qFDQvz


The New Threat
   Robert A. Wilson, MD

• Intentional release of a virus, bacteria,
  or toxin upon a population with the
  purpose of causing wide scale illness
  or death and resulting in a state of
 History of
         History: Remote
• 600 BC - Assyrians contaminated enemy
  wells with Rye ergot.
• 1346 - Tartar army catapult bodies of
  plague victims over city walls of Kaffa,
• French and Indian War - British gave
  American Indians blankets infected with
          History: Recent

• 1969 - President Nixon halts all U.S.
  Biological Weapons Research.
• 1975 - Convention on the Prohibition of the
  Development, Production, and Stockpiling
  of Bacteriological and Toxin Weapons and
  on their Destruction went into effect.
          History: Recent

• 1979 - Sverdlovsk, former USSR - 68
  deaths from 79 cases of inhalational anthrax
  follows accidental release of aerosolized
  anthrax spores.
• 1984 - The Dallas, Oregon - 751 cases of
  Salmonellosis, 44 hospitalized after
  Rajneeshpuram cult contaminated 2 local
  salad bars with Salmonella Entiritidis.
          History: Recent
• 1995 - Tokyo, Japan - Aum Shinrikyo cult
  released Sarin in subway station. Previous
  attacks with Anthrax and Botulism were
• 1999 - West Nile Virus outbreak in New
  York, New York. (Possibly due to
• 2001 - 12 Cases of Inhalational Anthrax , 5
  deaths following mail-based anthrax attack.
         Impact of an Attack
• 1970 - WHO (World Health Organization)
  estimates 250,000 deaths following aerosolized
  attack with 50 kg of Anthrax spores over city
  of 5 million.
• 1993 - U.S. Congressional Office of
  Technology Assessment estimates 1,300,000 to
  3 million deaths after aerosolized attack of 100
  kg of Anthrax on Washington D.C..
• Match or exceed Hydrogen Bomb of 1.0
  Megaton over same area
        Impact of an Attack

“Dark Winter” - Biological war game
 played in early part of 2001
 Variola Major (smallpox) virus released in
  3 states.
 No disease was detected for 9 days
 After 13 days, thousands were infected in
  25 states and 15 countries.
           Impact of an Attack
               Senator Sam Nunn
       - Senate Defense Expert Observer -
 Raised doubts about U.S. ability to respond and contain
   such an epidemic.
 U.S. hospitals lacked isolation rooms, infection control
 Poor communication between local, state, and national
 15 million vaccine doses were inadequate.
        Impact of an Attack

• May 2000 - Exercise in which terrorist
  sprayed concert with plague in Denver, CO.
  – 1000 people died but participants were able to
    contain epidemic.
• Wetter et al - Invoke theoretical attack with
  anthrax causes 32,000 deaths.
  – Survey of hospital Emergency Departments in
    4 states demonstrate a lack of preparedness for
    effective treatment.
             The Threat
 Category A - Agents most likely to cause
  mass casualties if deliberately disseminated;
  generally as aerosol.
 Category B - Agents moderately easy to
  disseminate with moderate morbidity and low
  mortality; could be used to contaminate
 Category C - Emerging agents that could be
  engineered for mass dissemination.
              The Threat:
      Critical Biological Agents
 –   Variola major (smallpox)
 –   Bacillus enthracis (anthrax)
 –   Yersinia pestia (plague)
 –   Clostridium botulinum toxin (botulism)
 –   Francisella tularensis (tularemia)
 –   Areneviruses
      • Lassa (lassa fever)
      • Junin (Argentine hemorrhagic fever)
 – Filoviruses
      • Ebola (ebola hemorrhagic fever)
      • Marburg (marburg hemorrhagic fever)
                 The Threat:
         Critical Biological Agents
    –   Coxiella burnetti (Q-fever)
    –   Brucella spp (burcellosis)
    –   Burkolderia mattei (glanders)
    –   Alphaviruses
    –   Ricin toxin from Ricinus communis (castor beans)
    –   Epsiton toxin of Clostridium perfingens
    –   Staphlococcus enterotoxin B
• A subset of Category-B agents includes pathogens that are spread
  by food and water. These pathogens include but are not limited to:
    –   Selmonella spp
    –   Shigella dysenteriae
    –   Escherichia coli 0157:H7
    –   Vibrio cholerae
    –   Cryptosporidium parium
                  The Threat:
          Critical Biological Agents
   –   Nipah virus
   –   Hantaviruses
   –   Tick-borne hemorrhagic fever viruses
   –   Tick-borne encephalitis viruses.
   –   Yellow fever
   –   Multidrug-resistant tuberculosis
• Preparedness for Category-C agents requires
  research to improve disease detection, diagnosis,
  treatment, and prevention
• ED physicians, physicians’ offices, and clinics
  will be the first responders.
• Epidemiological Warning networks such as
  hospitals, local, state, and national public health
  agencies will collect, analyze, and disseminate
• EMERGency ID NET and The Food borne disease
  Active Surveillance Network could act as
  framework for “syndrome surveillance”
• Key to recognition is a high index of suspicion.
     Features Indicative of Bioterrorism
• Multiple simultaneous patients with similar clincal
• Severe illness, especially among the young and otherwise
  healthy individuals
• Predominantly respiratory symptoms (if that was the route of
• Unusual (nonendemic) organism(s)
• Unusual antibiotic resistance patterns
• Atypical clinical presentation of disease
• Unusual patterns of disease such geographic co-location of
• Intelligence information: tips from law enforcement,
  discovery of delivery devices, etc.
• Reports of sick or dead animals or plants
Rapid Laboratory Confirmation
Tier based Laboratory Network
   Level A labs refer suspicious isolates and samples to higher level
        county or state laboratories.
    CDC provides a rapid response and advanced technology laboratory.
        - Process samples from suspect cases
        - Provide round the clock diagnostic support to bioterrorism
          response teams.
        - Help maintain chain of custody
        - Assess new rapid diagnostic assays before dissemination to
          laboratory network.

             Specimen testing and referral    Level D: Diagnosis Rare
             Training and Consultation                 Agents

                                             Highest level of Containment
                                                     and Expertise
Level C: Rapid Identification

 Level B: Agent Isolation

 Level A: Early Detection
 Analyze incoming data from the field perhaps
  through a single nationwide toll free number, 24-
  hour hot line.
 Contact appropriate authorities to initiate a
  response to include the FBI, FEMA, OEP, and
  Metropolitan Medical Response System for
  individual cities.
 Rapid dissemination of public health information
  through media
      - Disease prevention information
      - Avoid possible public panic
Roles of National Organizations
   FBI (Federal Bureau of Investigation)
      - Collect evidence for possible arrests and prevention of future
   FEMA (Federal Emergency Management Agency)
      - Coordinates disaster consequence management.
   OEP (Office of Emergency Preparedness)
      - Coordinates all direct medical assistance.
   Metropolitan Medical Response System
      - Teams of local personnel from 120 major cities.
      - First responders to a local disaster with help of state
        military units.
   CDC (Center of Disease Control)
      - Provides advice and support to all agencies involved.
           Health Care Defense
 Decontamination
  - Not effective or necessary for aerosol exposures.
  - Patients may shower at home.
  - Skin contamination - wash patient with soap and water, surfaces may
    be washed with dilute bleach (0.5% hypochlorite)
 Isolation
  - Any patient with respiratory or skin rashes should have respiratory
    and contact precautions.
  - Smallpox requires HEPA mask (High Efficiency Particulate Air).
  - Pneumonic Plague requires “droplet precautions”.
  - Viral hemorrhagic fevers requires strict barrier precautions.
        Treatment of Patients

• Hospitals must have access to pharmaceuticals and
  supplies in large quantities.
• CDC will coordinate regional antibiotic and
  vaccine stockpiles under National Pharmaceutical
  Stockpile Program.
• “Push Packs” will be delivered by regional airlift
  on 24-hour call.
• Incorporate all public and willing private
  institutions including the VA system.
          Psychiatric Impact

• Survivors of any disaster may require prolonged
• 1/3 of all hospitalized patients following Tokyo
  Sarin attack suffered psychiatric problems.
• 26% of local population following Three Mile
  Island meltdown suffered from psychiatric
  disorder 18 months later
• Following tragedy, 75% are temporarily
  bewildered, 25% become hysterical or paralyzed
  by fear.
         Psychiatric Impact

 Therapists should provide crisis intervention to
      - Psychologic debriefing within hours or days
      - Encourage survivors to verbalize their
        experiences and concerns
      - Spend time with injured and frightened
      - Help reunite children with parents
      - Refer psychiatric disorders for
            Preparedness Planning and
              Readiness Assessment
Current Level of Preparedness not acceptable
 Recent study by Wetter et al evaluated US hospitals level
  of preparedness for Biological Attack.
  - Only 12% met the study’s minimal requirements for
  - 1/2 of hospitals did not have a decontamination unit
       (Portable or ED).
  - 62% did not have pralidoxime for possible sarin attack.
  - Only 1/2 hospitals had enough Cipro or Doxycycline
       for 2-day supply for 50 patients.
  - Fewer than 20% had plans for Biological/Chemical
           Preparedness Planning and
             Readiness Assessment
Necessary steps to enhance Preparedness
 All hospitals require either portable or isolated ED
  decontamination unit.
 Access to large quantities of medication locally.
 Respiratory Protection and Chemical protection
 Chemical/Biological attack plan with defined
  performance standards.
 Regular training to meet standards.
  PDLS (Physician Disaster Life Support).
         Preparedness Planning and
           Readiness Assessment

 Types of disaster and Initial Triage
 Prehospital Management
 Hospital Disaster Management
 Terrorism - NBC and conventional.
 Personal/Family Preparedness
 Types of

•   Disease produced by Bacillus anthracis.
•   High Mortality.
•   Relatively easy to manufacture.
•   Long term storage in spore form.
•   Easy to weaponize and disseminate
• 3 types of Anthrax
   – Cutaneous – most common
     (2000 cases annually)
   – GI – follows ingestion of
     insufficiently cooked,
     infected meat
   – Inhalational – very rare but
     high mortality
• Commonly occurs in
• Wool and goat skin
  workers traditionally at
  high risk.

                   Inglesby TV, et al. for the Working Group on Civilian Biodefense JAMA. 1999;281:1735-1745
           Anthrax: Microbiology

• Aerobic, gram positive,
  spore-forming, nonmotile
• Bamboo rod appearance
• Spores form in nutrient
  poor environment

                   Inglesby TV, et al. for the Working Group on Civilian Biodefense JAMA. 1999;281:1735-1745
          Anthrax: Inhalational
• Caused by inhalation of spores
• Pathogenesis
   –   Deposition of spores in alveolar spaces.
   –   Macrophages ingest spores.
   –   Transported via lymphatics to mediastinal lymph nodes.
   –   Leads to release of toxins.
   –   Causes hemorrhagic mediastinal lymphadenitis
   –   May cause concurrent hemorrhagic meningitis
   –   Overwhelming sepsis and shock
                Anthrax: Inhalational
• Clinical presentation – 2 Stages
• Stage 1
    – Mediastinal Widening
    – Spectrum of nonspecific
    – Fever, dyspnea, cough, abdominal
      and chest pain, weakness, and
• Stage 2
    – Rapidly fulminant stage
    – Fever, dyspnea, cyanosis,
      meningimus, delerium
    – Rapid progression of shock to
• Mortality rate of 89% in US

                          Inglesby TV, et al. for the Working Group on Civilian Biodefense. JAMA. 1999;281:1735-1745
       Anthrax: Inhalational

Physiological Sequella of Severe Infection
• Hypoglycemia/Hypokalemia
• Depression of Respiratory Center
• Anoxia/ Respiratory Alkalosis
• Hypotension/Terminal Acidosis
              Anthrax: Cutaneous

• Infection follows
  deposition into previous
• Pruritic macule
  progresses to vesicle and
  then to round ulcer (Day
• Forms painless, black
  escar; heals in 1-2 weeks
• Without antibiotics, 20%
  will develop systemic
  anthrax and die

• Results from ingestion of insufficiently cooked,
  infected meat
• Oral Pharyngeal or esophageal ulcers
   – Can lead to regional adenopathy, sepsis, and death.
• Terminal ileum or ceceum
   – Causes nausea, vomiting, and diarrhea
   – Progresses to bloody, diarrhea, massive ascites, acute
     abdomen and death.
         Anthrax: Diagnosis

• Sudden appearance of large number of patients
  with flu-like symptoms and high mortality rate.
• Rapid diagnostic test (Mayo Clinic recently
  developed 5 minute Antigen Assay).
• Recognition of widened mediastrium with
  associated overwhelming flu.
• Sputum or blood analysis – gram-positive bacillus
• Post mortem evidence of thoracic hemorrhagic
  necrotizing lymphadenitis or hemorrhagic
        Anthrax: Transmission

• Inhalation of spores
• Direct contact
• Ingestion of infected
• No person to person
              Anthrax: Treatment
• Treat all suspected cases initially with Ciprofloxin, Doxycycline,
  or PCN G.
• Delay of antibiotic even for a few hours may decrease chance for
• Initial studies on monkeys done with Ciprofloxin and Doxycycline.
• Treatment for 60 days – Inhibit secondary or tertiary infections.

                                          Sverdlovsk accidental
                                          exposure to Anthrax
           Anthrax: Vaccine
• US Anthrax – Inactivated Cell-Free filtrate produced
  by Bioport Corp.
• Principal antigen is the protective antigen.
• A human live attenuated vaccine is produced and used
  in countries of former Soviet Union
• Study of experimental monkeys demonstrated high
  rate of protection.
• 590,000 doses have been given to US Armed Forces
  with minimal side effects and no serious causal
• Post exposure vaccination is recommended if
  available after known attack
    Treatment of Special Groups
• Children less that 6 years old
  – Ciprofloxin initially then change to PCN after
    susceptibility testing.
  – Doxycycline should be used initially if
    Ciprofloxin not available.
  – Pregnant Women/ Immunocompromised –
    same as children
         Anthrax: Treatment

Recent Study by Shin et al, in Cell Biology and
• Treatment with DHEA (dihydroepiandosterone)
  and melatonin decreased release of TNF (tumor
  necrosis factor).
• TNF is responsible for necrotic lymphadenitis.
• May have a therapeutic role in late infection.

• Caused by Variola Major or Minor, large DNA
• Routine vaccinations stopped in the United States
  in 1972.
• Declared eradicated in 1980
• Protective Factor vaccine estimated to be
  approximately 10 years
• 15 million doses in United States, 20 million
  stored at WHO

• Incubation- Usually 12-14 days, Range 7-17
• Symptoms
  – High fever, myalgias, malaise, vomiting, and headache.
  – Abdominal pain
  – Followed by synchronous rash which progresses from:

  Macules           Papules           Pustular lesions
• Signs
   – Synchronous rash,
     progresses from extremities
     and face to trunk
   – Pocks seen on palms and
   – Involves mucous
• Transmission
   – Person to person, airborne,
     or direct contact
   – Highly transmissible after
     patient becomes febrile or
     until all lesions resolved

                  Henderson DA, et al. for the Working Group on Civilian Biodefense JAMA. 1999;281:2127-2137
          Smallpox: Comparsion

      Smallpox                  Chickenpox
• Palms and soles         • Seldom on palms or
• Begins on face/ext      • Begins on trunk
• Synchronous evolution   • Asynchronous evolution
• Fever and malaise 2-4   • No fever prior to rash
  days prior to rash
        Smallpox: Treatment

• Index case and all contacts should be quarantined
  for 17 days or until resolution
• Vaccination recommended within 4 days of
• Vaccine and Vaccina Immune Globulin (VIG)
  recommended if more than 1 week elapsed
• All immunocompromised or exfoliative skin
  disorders should be given VIG
• Cidofir has shown significant in vitro and in vivo
  activity in animals
• Infectious disease carried by
• Two forms
               Plague: Pneumonic

• Spread by droplet through
  respiratory exposure
• Incubation time: 2-3 days
• Symptoms – Sudden onset of
  fever, chills, headache,
  vomiting, diarrhea, purpura,
  cough with hemoptysis
• Signs – Bronchopneumonia
  with patchy or consolidated
• Progression to sepsis, dyspnea,
  respiratory and circulatory
• Death 12-24 hours if not treated

                    Inglesby TV, et al. for the Working Group on Civilian Biodefense. JAMA. 2000;283:2281-2290
                Plague: Bubonic
• Spread by vector or
  hemotogenous spread
• Incubation: 2-3 days
• Symptoms
   – High fever, severe headache,
     nausea/vomiting and rigors
   – Altered mentation, abdominal
     pain, and chest pain
• Signs
   – Bubo formation in 6-8 hours
     especially in groin, axilla or
     cervical areas
   – Tachycardia, hypotension, and

                   Inglesby TV, et al. for the Working Group on Civilian Biodefense. JAMA. 2000;283:2281-2290

• Diagnosis
  – Culture of sputum, bubo aspirate, blood, or
  – Serum Immunoassays
  – Suspect if large numbers of fulminant gram
    negative pneumonia
• Mortality – 50%
        Plague: Treatment

• Streptomycin in 30 mg/kg/day; IM daily in
  2 divided doses
• Doxycycline 100 mg po every 12 hours
• Gentamycin 5 mg/kg IV/IM daily
• Chloramphenicol 15 mg/kg IV 4 times per
  day for meningitis
• Prophylactic Doxycycline for known

•   Toxin produced by Clostridium Botulinum
•   Neurotoxin which blocks release of acetylcholine
•   15,000 times more potent than Sarin gas
•   Symptoms
    – Cranial nerve palsies such difficulty speaking or
    – Descending paralysis, generalized weakness, progresses to
      respiratory failure

                   Arnon SS, et al. for the Working Group on Civilian Biodefense JAMA. 2001;285:1059-1070

• Signs
   –   Dilated or unreactive pupils
   –   Drooping eyelids
   –   Diploplia
   –   Slurred speech
   –   Descending paralysis with
       intact mental status
• Transmission
   – Aerosol inhalation
   – Food ingestion
   – No person to person spread
        Botulism: Treatment

• Botulinum Equine Antitoxin A, B, C, D, or E.
• Supportive therapy – Mechanical ventilation
  Experimental vaccine has been used in high-risk
  lab workers and military
• Vaccine is NOT effective post-exposure
• Decontaminate individuals with soap and water
• Surface decontamination with heat or a chlorox
  solution (bleach)

• Aerosolized Francisella Tularenis can
  cause systemic illness and pneumonia
• Incubation: 3-10 days
• Symptoms
  – Flu-like illness
  – Cough with associated pleuritic pain
  – Rare hemoptysis

• Signs
   – Bilateral patchy infiltrates
     with associated hilar
     adenopathy and pleural
   – Diffuse, varied rash
• Mortality – 35% without
• Transmissions
   – Inhalational
   – No person to person

                   Dennis DT, et al. for the Working Group on Civilian Biodefense JAMA. 2001;285:2763-2773
        Tularemia: Treatment

• Live attenuated vaccine available but NOT
  recommended post-exposure
• Gentamycin, Streptomycin, or IV
  Ciprofloxin once symptomatic
• Prophylaxis with Ciprofloxin, Doxycycline,
  or Tetracycline during incubation for
  possible exposure
    Viral Hemorrhagic Fevers

• Include Ebola, Marburg, Lassa,
  and Congo Crimean
• Incubation periods vary
• Transmission
  – Contact with infected blood or
    Viral Hemorrhagic Fevers
• Symptoms
  – Fever/chills, flushing, myalgias, dizziness, and
  – Nausea, vomiting, and diarrhea
  – Petechia, bleeding, and edema
• Signs
  – Disseminated Intravascular Coagulopathy
  – Hypotension and shock
• Mortality – 50-80%
       Viral Hemorrhagic Fevers
• Intensive supportive care with hemodynamic
• Ribarvirin IV – Lassa fever
• Investigational vaccine is available.
• Isolation – most require anteroom and contact
• Ebola, Marburg, Lassa, and Congo Crimean require
  negative air pressure room, respiratory isolation with a
  HEPA mask, and contact precautions.
• Surfaces should be cleaned with a chlorine solution
• Lab specimens double bagged and exterior cleaned.
• Extreme caution with all sharps.
          Role of the
     Primary Care Physician

• Have a high level of suspicion
   – Keep bioterrorism agents in differential diagnosis
• Recognize typical bioterrorism syndromes
• Be aware of unusual epidemiologic trends
• Know treatment/prophylaxis of bioterrorism
• Know how to report suspected bioterrorism

To top